Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 317
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artif Cells Nanomed Biotechnol ; 48(1): 435-442, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31916466

RESUMO

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

2.
Int J Biol Macromol ; 147: 170-176, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923511

RESUMO

Bacterial UDP-N-acetyl-d-glucosamine:heparosan alpha-1, 4-N-acetyl-d-glucosaminyltransferases (KfiAs) are in high demand for the development of animal-free heparin (HP) production. Until now, EcKfiA from Escherichia coli O10:K5:H4 was the sole identified member of this family. The lack of known members has limited research into molecular structure and catalytic mechanism of the KfiA superfamily, and restricted its application in enzymatic glycan synthesis. Herein, we report the identification and characterization of Gallibacterium anatis GaKfiA, doubling the number of known members of the KfiA family. GaKfiA is a monofunctional enzyme that transfers N-acetyl-d-glucosamine (GlcNAc) residues from their nucleotide forms to the nonreducing ends of saccharide chains structurally equivalent to the backbone of HP. The catalytic efficiency of GaKfiA is lower than that of EcKfiA. However, a single mutation of GaKfiA, N56D, resulted in a drastic increase in kcat/Km compared with wild-type GaKfiA. These data once again indicate the key role of a complete DXD motif for the catalytic efficiency of glycosyltransferases. This study deepens understanding of the mechanism of KfiA, and will assist in research into animal-free HP production.

3.
Echocardiography ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786807

RESUMO

OBJECTIVES: To evaluate whether inferior vena cava compression (IVCC) can be an alternative for valsalva maneuver (VM) in contrast-enhanced transcranial doppler (c-TCD). METHODS: Patients diagnosed with ischemic stroke, transient ischemic attack, and migraine were enrolled in this study. C-TCD was conducted at resting state, after VM and IVCC to detect right to left shunt (RLS). Then, the RLS was compared to examine whether IVCC could be an alternative for VM in c-TCD. RESULTS: A total of 246 patients were enrolled in this study. Via Wilcoxon signed-rank test of paired data, the detection for RLS of c-TCD conducted after IVCC was superior to at resting state, but inferior to after VM (P ï¼œ .001, P = .01, respectively); the detection for RLS of c-TCD conducted after IVCC was inferior to after VM for patients with good cooperation of VM, but was superior for patients with poor cooperation of VM (P ï¼œ .001, P ï¼œ .001, respectively); the detection for RLS of c-TCD conducted after IVCC and after VM showed no significant difference for patients with good cooperation of VM and without abdominal obesity, or with poor cooperation of VM and with abdominal obesity (P = .201, P = .157, respectively); the detection for RLS of c-TCD conducted after IVCC was superior to at resting state for patients with abdominal obesity (P ï¼œ .001). CONCLUSIONS: For patients with poor cooperation of VM, IVCC could be used as an effective supplement to increase the detection of RLS in c-TCD.

4.
Huan Jing Ke Xue ; 40(12): 5234-5239, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854593

RESUMO

With the retrofitting of coal-fired power plants and steel plants for ultra-low-emission control, the concentration of filterable particles (FPM) from these sources is decreasing gradually. The condensable particle matter (CPM) draws more attention. The understanding of CPM emission concentration and chemical characteristics is still limited. There has been no standard determination method of CPM in China until now. In this study, three methods, including the dry impinger method (US EPA method 202), indirect dilution method, and direct dilution method, are discussed and compared in measuring CPM emissions from coal-fired power plants, coke-making plants and sintering plants. The results show that method 202 overestimates the emissions of CPM, due to the fact that the gaseous HCl or SO2 dissolves into condensable liquid and cannot be completely eliminated by N2 purging after sampling. Instead, CPM measured using the indirect dilution method better represents its real emission levels into the atmosphere.

5.
Huan Jing Ke Xue ; 40(8): 3457-3462, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854750

RESUMO

Wet flue gas desulphurization (WFGD) is wildly used to control SO2 emission from coal-fired power plants. The influence of WFGD on particulate matter (PM) emission has recently drawn significant public attentions in China. In this study, PM2.5 was collected at both the inlet and outlet from three WFGD units, including a single scrubber lime-stone-gypsum FGD unit, a cascade scrubber lime-stone-gypsum FGD unit, and a seawater FGD unit. PM2.5 mass concentrations and their chemical compositions were analyzed. A method to calculate the addition and removal ratios is proposed according to the concertation of PM2.5 components, such as Ti, Pb, Cr, and V. The results indicate that the removal ratio was similar between the three WFGD units (77.1% on average). However, the addition ratio varied significantly. The performance of the cascade scrubber lime-stone-gypsum FGD unit was best, with a lower addition ratio of 8.6%, which is attributed to the weaker evaporation of desulphurization slurry droplets in their second tower under the low temperature of the flue gas. The addition ratio of the seawater FGD unit was also low (23.9%) because of its low concentration of solids in the seawater. The addition ratio of the single scrubber lime-stone-gypsum FGD system was highest, with a value of 162.3%, which was probably due to the low efficiency of the de-mister.

6.
Phys Rev E ; 100(5-1): 053107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31869921

RESUMO

A direction adaptive approach for the reduction of drag and the suppression of lift fluctuation in flow passing a circular cylinder is developed. Flexible filaments are attached to the surface of the cylinder, and different configurations, including the number, lengths, and angles of attachment of the filaments, as well as their tension and bending features, are investigated. In this comprehensive numerical study, the configuration with two filaments 180^{o} apart is found to be optimal for drag reduction and lift fluctuation suppression and is adaptive to the direction of the incoming flow. A drag reduction of 10.8% and a lift fluctuation suppression of 34.6% can be achieved as one filament is attached to the rear stagnation point and the other to the front stagnation point. The hairy coating resembled by 12 evenly attached filaments is also considered. Though marked drag reduction has not been found for this configuration, we leave it an open question for future studies to explore various properties of the filaments in turbulent flow, whose interaction with the filaments would be significant.

7.
Huan Jing Ke Xue ; 40(10): 4497-4504, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854817

RESUMO

To clarify the spatial distribution and pollution status of nutrients in the surface sediments from a macrophyte-dominated zone in Lake Taihu, total nitrogen (TN), total phosphorus (TP), alkali nitrogen (AN), available phosphorus (AP), and organic matter (OM) were measured at 60 sampling sites in Xukou Bay. A pollution evaluation and source apportionment analysis of these nutrients was also carried out. The average contents of TN, TP, AN, AP, and OM in the surface sediments of Xukou Bay were 1027.5, 423.2, 46.4, 15.3, and 17096.6 mg·kg-1, respectively, with the OM content being significantly higher in the northeast zone than in other areas of the bay. The average value of STN and STP was 1.75 and 0.91, respectively, indicating that TN and TP represent moderate and mild levels of pollution, respectively. The average comprehensive pollution index (FF) was 1.57, indicated that the surface sediment was moderately polluted. The observed organic pollution index indicated that the surface sediments in Xukou Bay were generally clean. Based on C/N values, organic matter in the surface sediments is derived from the bio-deposition of non-fibrous plants and phytoplankton. Based on correlation analysis, OM and TN in the surface sediments of Xukou Bay are derived from the same source, while TP is derived from an alternative source.


Assuntos
Lagos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Nitrogênio , Nutrientes , Fósforo
8.
Adv Exp Med Biol ; 1209: 79-108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728866

RESUMO

Pattern recognition receptors (PRRs) are sensors of exogenous and endogenous "danger" signals from pathogen-associated molecular patterns (PAMPs), and damage associated molecular patterns (DAMPs), while autophagy can respond to these signals to control homeostasis. Almost all PRRs can induce autophagy directly or indirectly. Toll-like receptors (TLRs), Nod-like receptors (NLRs), retinoic acid-inducible gene-I-like receptors (RLRs), and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway can induce autophagy directly through Beclin-1 or LC3-dependent pathway, while the interactions with the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1), CD91/Calreticulin, and TLRs/HSPs are achieved by protein, Ca2+, and mitochondrial homeostasis. Autophagy presents antigens to PRRs and helps to clean the pathogens. In addition, the induced autophagy can form a negative feedback regulation of PRRs-mediated inflammation in cell/disease-specific manner to maintain homeostasis and prevent excessive inflammation. Understanding the interaction between PRRs and autophagy in a specific disease will promote drug development for immunotherapy. Here, we focus on the interactions between PRRs and autophagy and how they affect the inflammatory response.


Assuntos
Autofagia , Inflamação , Receptores de Reconhecimento de Padrão , Autofagia/imunologia , Humanos , Receptores de Reconhecimento de Padrão/metabolismo , Transdução de Sinais
9.
Adv Clin Exp Med ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31782272

RESUMO

BACKGROUND: Rapamycin inhibits the mammalian target of rapamycin (mTOR) activity and has been proven effective for the treatment of lung injury. OBJECTIVES: The objective of this study was to investigate the roles of the mTOR pathway and its inhibitor rapamycin in the repair of hyperoxia-induced acute lung injury (ALI). MATERIAL AND METHODS: Firstly, premature rat lung fibroblast L929 cells were cultured under different oxygen concentrations (40%, 60%, and 90%). At day 3, 7 and 14 after exposure, MTT assay and flow cytometry were used to evaluate the effect of oxygen stress on cell viability and apoptosis of L929 cells, respectively. Secondly, microscopy, MTT assay and flow cytometry was used to investigate the effect of 10 nM rapamycin on 90% O2 exposed L929 cells. We also used small interfering RNAs (siRNAs) to abrogate the expression of mTOR in 90% O2 exposed L929 cells, and then evaluated the apoptosis and cell viability using flow cytometry and the MTT assay, respectively. In addition, western blot was used to detect the protein expression of Bcl-2, p53, TGF-ß and connective tissue growth factor (CTGF). A hyperoxia-induced lung injury model was established in Sprague Dawley (SD) rats in order to evaluate the histopathological changes in lung tissues and expression of the mTOR pathway and fibrosis related factors. RESULTS: Exposure to 40%, 60% or 90% oxygen all significantly inhibited the growth of L929 cells. Application of 10 nM rapamycin was found to effectively promote apoptosis of 90% O2 exposed L929 cells. In addition, mTOR siRNA promoted the apoptosis and inhibited the growth of L929 cells. Rapamycin inhibited the activation of the mTOR signaling pathway, down-regulated the expression of downstream proteins p70S6K and 4EBP1, reduced the collagen deposition and the production of fibrosis-inducing factors, including TGF-ß and CTGF in hyperoxia-induced lung injury rats. CONCLUSIONS: Rapamycin may be useful for the treatment of hyperoxia-induced acute lung injury (ALI) by inhibiting the activation of mTOR signaling pathway.

10.
BMC Infect Dis ; 19(1): 939, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699043

RESUMO

BACKGROUND: Invasive candidiasis (IC) is the most common invasive fungal infection. The epidemiology of IC in hospitalized patients has been widely investigated in many metropolitan cities; however, little information from medium and small cities is known. METHODS: A 5-year retrospective study was carried out to analyze the prevalence, species distribution, antifungal susceptibility, risk factors and mortality of inpatients with invasive Candida infection in a regional tertiary teaching hospital in Southwest China. RESULTS: A total of 243 inpatients with invasive Candida infection during the five-year study period were identified, with a mean annual incidence of 0.41 cases per 1000 admissions and a 30-day mortality rate of 12.3%. The species distributions of Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, Candida parapsilosis and other Candida species was 45.3, 30.0, 15.2, 4.9, 2.1 and 2.5%, respectively. The total resistance rates of fluconazole (FCA), itraconazole (ITR) and voriconazole (VRC) were 18.6, 23.1 and 18.5%, respectively. Respiratory dysfunction, pulmonary infection, cardiovascular disease, chronic/acute renal failure, mechanical ventilation, abdominal surgery, intensive care in adults, septic shock and IC due to C. albicans were associated with 30-day mortality (P < 0.05) according to the univariate analyses. Respiratory dysfunction [odds ratio (OR), 9.80; 95% confidence interval (CI), 3.24-29.63; P < 0.001] and IC due to C. albicans (OR, 3.35; 95% CI, 1.13-9.92; P = 0.029) were the independent predictors of 30-day mortality. CONCLUSIONS: This report shows that the incidence and mortality rates are lower and that the resistance rates to azoles are higher in medium and small cities than in large cities and that the species distributions and risk factors in medium and small cities are different from those in large cities in China. It is necessary to conduct epidemiological surveillance in medium and small cities to provide reference data for the surveillance of inpatients with IC infections.

11.
Twin Res Hum Genet ; : 1-4, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31708009

RESUMO

The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.

12.
Medicine (Baltimore) ; 98(44): e17780, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689845

RESUMO

RATIONALE: Foreign bodies related ureteral obstruction and hydronephrosis is rare and usually cause numerous problems for clinical physicians. PATIENT CONCERNS: We report a 36-year-old female who was referred to our hospital due to a 4-year history of dull pain on the left back. DIAGNOSIS: X-ray and abdominal CT revealed a foreign body around the upper part of the left ureter with ureteral obstruction and hydronephrosis. INTERVENTIONS: Laparoscopy was performed and a 3-cm sewing needle was removed successfully. OUTCOMES: After 6 months' follow-up, the patient's ureteral obstruction and hydronephrosis were significantly reduced, and the double-J ureteral stent was removed. LESSONS: This case indicated that ureteral obstruction and hydronephrosis caused by foreign bodies needed to be early diagnosed and located. Invasive therapies rather than conservative treatments are preferred to remove the FBs and relieve obstruction.


Assuntos
Corpos Estranhos/complicações , Hidronefrose/etiologia , Laparoscopia/métodos , Ureter/lesões , Obstrução Ureteral/etiologia , Adulto , Feminino , Corpos Estranhos/cirurgia , Humanos , Hidronefrose/cirurgia , Laparoscopia/instrumentação , Stents , Ureter/cirurgia , Obstrução Ureteral/cirurgia
13.
Nano Lett ; 19(11): 7866-7876, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31594301

RESUMO

Nanoscale photodynamic therapy (PDT) is an appealing antitumor modality for which apoptosis is the major mechanism of toxicity induction. It was postulated that the highly reactive singlet oxygen in PDT could deplete glutathione (GSH) and activate ferroptosis, the extent to which could be further manipulated by a redox-responsive nanocarrier. To validate this, a disulfide-bearing imidazole ligand coordinated with zinc to form an all-active metal organic framework (MOF) nanocarrier where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless of light irradiation, the Ce6-loaded nanocarrier caused the depletion of intracellular GSH via the disulfide-thiol exchange reaction in a murine mammary carcinoma cell line (4T1). The GSH depletion further caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement of cytotoxicity that was alleviated by ferroptosis inhibitors. The superior in vivo antitumor efficacy of the all-active nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression and animal survival rate. The coadministration of an iron chelator weakened the antitumor potency of the nanocarrier due to ferroptosis inhibition, which was supported by the fact of tumor growth upsurge and the recovered GPX4 activity. The current work highlights the contribution of ferroptotic machinery to antitumor PDT via an activatable, adaptable, all-active MOF nanocarrier.

14.
Front Physiol ; 10: 1256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611820

RESUMO

Spodoptera exigua and S. litura are two sympatric species in China and many other countries. Both moths employ a multiple component sex pheromone blend, including a common component Z9,E12-14:OAc, and two specific components Z9-14:OH and Z11-16:OAc for S. exigua, and one specific component Z9,E11-14:OAc for S. litura. For the two species, it has been well documented that males are able to recognize and behaviorally attracted by their species-specific sex pheromone, which functions as a means of reproductive isolation, but whether males could mutually recognize pheromone components of its sympatric species is unknown. In the present study, the electroantennogram (EAG) and field evaluation were conducted to address this topic. The EAG recordings revealed that males of each species could significantly respond to specific components of its sympatric species, although the response values were lower than that to its own major component. In field tests, the specific components Z9-14:OH and Z11-16:OAc of S. exigua strongly inhibited the male catches of S. litura to its conspecific sex pheromone, while specific component Z9,E11-14:OAc of S. litura significantly reduced the male catches of S. exigua to its sex pheromone. Furthermore, the combined lure of the two species completely inhibited male catches of S. litura, and significantly decreased the male catches of S. exigua, compared to the species-specific lure alone. The results demonstrated that males of the two sibling species could perceive the specific components of its counterpart, suggesting that mutual recognition of pheromone components may function to strengthen the behavioral isolation between the two species. Our study has added new knowledge to the reproductive isolation via sex pheromone communication system in sympatric moth species, and provided a base for designing of mating disruption tactics targeting multispecies by using insect sex pheromones.

15.
Sleep Med ; 63: 82-87, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31606653

RESUMO

OBJECTIVE: To evaluate the effect of insomnia after acute ischemic stroke on cerebrovascular reactivity (CVR). METHODS: A total of 158 eligible patients with acute ischemic stroke were enrolled prospectively. Of these, six patients were lost to follow-up, and 152 were included in the final analysis. The patients were divided into the insomnia (N = 24) and non-insomnia (N = 128) groups based on the Athens Insomnia Scale. The insomnia group was further divided into benzodiazepine (BDZ) and non-BDZ treatment groups according to BDZ use status after ischemic stroke. The transcranial doppler ultrasound (TCD) breath-holding test was performed to calculate the breath-holding index (BHI) of the responsible cerebral middle artery, which was used to evaluate CVR. Then, univariate and multivariate linear regression analyses were carried out to determine the effect of insomnia after acute ischemic stroke on CVR. RESULTS: At one month after the onset of acute ischemic stroke, TCD-BHI was significantly higher in the non-insomnia group compared with the insomnia group (p = 0.027). In patients with insomnia, TCD-BHI was significantly higher in the BDZ treatment group compared with non-BDZ treatment group (p = 0.039). With age, hypertension, diabetes, hyperlipidemia, long-term smoking, blood homocysteine, and Athens Insomnia Scale score as independent variables, and TCD-BHI at one month after onset as a dependent variable, univariate and multivariate linear regression analyses indicated that the Athens Insomnia Scale score was an independent factor affecting TCD-BHI (regression coefficient, -0.013; 95% confidence interval (CI) -0.024 to -0.003). CONCLUSION: Insomnia after acute ischemic stroke is an independent risk factor for CVR.

16.
mSphere ; 4(5)2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484738

RESUMO

The demand for a prophylactic vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has motivated numerous dedicated research groups to design and develop such a vaccine. In this study, we have developed a multivalent vaccine, Sta-V5, composed of five conserved antigens involved in three important virulence mechanisms. This prototype vaccine conferred up to 100% protection against multiple epidemiologically relevant S. aureus isolates in five different murine disease models. The vaccine not only elicits functional antibodies that mediate opsonophagocytic killing of S. aureus but also mounts robust antigen-specific T-cell responses. In addition, our data implied that γδ T cells contribute to the protection induced by Sta-V5 in a murine skin infection model.IMPORTANCE Staphylococcus aureus infections, especially MRSA infections, are becoming a major global health issue and are resulting in mortality rates that are increasing every year. However, an effective vaccine is lacking due to the complexity of the infection process of S. aureus In this study, we found that the addition of two novel protein components to three well-studied vaccine candidates significantly improved the efficacy of the combined vaccine. Furthermore, the five-component vaccine not only elicits a robust antibody response but also induces cytokine secretion by T cells, making it a promising vaccine candidate to fill the void.

17.
Biomaterials ; 223: 119486, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520887

RESUMO

Drug-tolerant persister cancer cells (PCCs) play an important role in the development of multidrug resistance (MDR) to anti-cancer drugs. This is due to the strong link between PCCs formation and epithelial-mesenchymal transition (EMT), as well as the low numbers of PCCs. In addition, PCC removal by traditional cytotoxic agents is poor due to the intrinsic high MDR activity in these cells. As a novel programmed cell death pathway, ferroptosis shows high potency to eliminate cells at the EMT state via manipulating intracellular redox homeostasis. The aim of this work was to utilize triggered ferroptotic polymer micelles for PCCs removal and MDR reversal both in vitro and in vivo. The micelles were made of arachidonic acid-conjugated amphiphilic copolymer that can enable rapid cargo release upon free radical-triggering in the tumor microenvironment. A potent ferroptotic inducer, RSL3 was encapsulated in the micelles to target the glutathione peroxidase 4 (GPX4). In the model resistant human ovarian adenocarcinoma cells, the RSL3 micelles were 30-fold more toxic than activatable control micelles due to the ferroptotic machinery. The lipid peroxidation-induced intracellular glutathione level reduction also made a contribution, which enhanced the potency of RSL3 for ferroptosis induction and enabled the drug-loaded micelles all-active. As an index of PCCs population, the level of CD133+ and aldehyde dehydrogenase (ALDH+) biomarker was significantly lower for the ferroptotic micelles in contrast to the control. The potency of ferroptotic micelles regarding PCCs reduction was proved by the in vitro soft agar colony forming assay. The in vivo anti-tumor efficacy of triggered micelles was further demonstrated in tumor-bearing nude mice in terms of PCCs biomarkers, tumor growth inhibition, mice survival, and GPX4 inhibition. This work demonstrates a novel strategy to overcome cancer MDR via the tailored ferroptotic micelles, which opens new avenues for managing resistant tumors.

18.
Genesis ; 57(11-12): e23335, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31513344

RESUMO

Dead-End 1 (DND1) encodes an RNA binding protein critical for viable primordial germ cells in vertebrates. When introduced into cancer cell lines, DND1 suppresses cell proliferation and enhances apoptosis. However, the molecular function of mammalian wild-type DND1 has mostly been studied in cell lines and not verified in the organism. To facilitate study of wild-type DND1 function in mammalian systems, we generated a novel transgenic mouse line, LSL-FM-DND1 flox/+ , which conditionally expresses genetically engineered, FLAG-tagged and myc-tagged DND1 in a cell type-specific manner. We report that FLAG-myc-DND1 is indeed expressed in specific tissues of the mouse when LSL-FM-DND1 flox/+ is combined with mouse strains expressing Cre-recombinase. LSL-FM-DND1 flox/+ mice are fertile with no overt health effects. We expressed FLAG-myc-DND1 in the pancreas and found that chronic, ectopic expression of FLAG-myc-DND1 led to increase in fasting glucose levels in older mice. Thus, this novel LSL-FM-DND1 flox/+ mouse strain will facilitate studies on the biological and molecular function of wild-type DND1.

19.
Org Biomol Chem ; 17(34): 7854-7857, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31408075

RESUMO

A copper-catalyzed DTBP oxidative dual C-H sulfurization has been developed for the direct thiocarbamation of imidazopyridines using a combination of elemental sulfur and formamides as carbamothioyl surrogates. NBS (bromo succinimide) was found to promote the thiocarbamation in good yields. This dual C-H sulfurization strategy enables access to a wide range of carbamothioyl imidazoheterocycles without the use of highly toxic phosgene.

20.
Adv Healthc Mater ; 8(18): e1900366, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365192

RESUMO

Traditional singlet oxygen-based antitumor therapies have been burdened with the necessity of external energy (e.g., light and ultrasound) and harmful dark toxicity. Ascorbate at the pharmacological concentration could accumulate hydrogen peroxide only in the tumor site. It is postulated that the concurrent delivery of ascorbate and nanoparticulate hypochlorous ion (ClO- ) could produce singlet oxygen at the tumor site as an energy-free, tumor-specific therapy. The ClO- is loaded in a hybrid core-shell nanocarrier consisting of a zeolitic imidazolate framework and amphiphilic poloxamer 188. Intracellular singlet oxygen production is verified in 4T1 cells by the cooperation between hybrid nanocarriers and ascorbate, which induces significant apoptotic cell death. Upon intravenous nanocarriers delivery plus intraperitoneal ascorbate administration to xenograft mice, the in vivo antitumor efficacy of this cooperative nanomedicine is demonstrated without noticeable side-effects. This work demonstrates a proof-of-concept of singlet oxygen-based chemodynamic therapy for selective tumor eradication, which produces a novel trigger-free, singlet oxygen-based cancer therapy without the side effects of traditional photodynamic and sonodynamic therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA